The objective of this project is to determine if structural and functional modifications of cell membranes in human tumors arise in the course of malignant transformation and if these changes in cell membranes may account for the abnormal cell-cell interactions which characterize malignant growth. The basic approach is to characterize specific membrane components, such as cell-cell junctions and certain classes of membrane proteins, in normal human epithelia and to compare these components with analogous components in human tumors which represent specific stages in the process of tumor development. Currently, our emphasis is on tumors arising in the human urinary bladder. In this tumor system, we have observed changes in 1- the numbers of cell-cell junctions per unit area of cell membrane and 2- alterations in the topographical distribution of cell membrane "integral" proteins which can be visualized by freeze-fracture electron microscopy. These quantitative changes in membrane components are being correlated with tumor grade and the biological behavior of each tumor (i.e. tumor stage). Preliminary data show that junctional frequency and protein molecular topography correlate well with grade and stage for a given tumor. Carcinogen induced rat urinary bladder tumors are being studied to determine the molecular mechanisms of the membrane changes that have been observed to arise in the course of human urinary bladder tumorigenesis.